Datopotamab deruxtecan application in the EU for patients with advanced nonsquamous non-small cell lung cancer voluntarily withdrawn
AstraZeneca and Daiichi Sankyo have voluntarily withdrawn the marketing authorisation application (MAA) in the EU for datopotamab deruxtecan (Dato-DXd) - a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo - for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) based on the TROPION-Lung01 Phase III trial.
The decision to withdraw the MAA was informed by feedback from the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA). AstraZeneca and Daiichi Sankyo will continue to work to bring datopotamab deruxtecan to patients with lung cancer in the EU who can benefit and are committed to unlocking the potential of this medicine in lung cancer.
AstraZeneca and Daiichi Sankyo’s application in the EU for datopotamab deruxtecan for the treatment of hormone receptor (HR)-positive, HER2-negative metastatic breast cancer based on the TROPION-Breast01 Phase III trial remains under review.
On January 13, 2025, AstraZeneca and Daiichi announced that the FDA has granted priority review to the US BLA seeking accelerated approval of datopotamab deruxtecan (Dato-DXd; TROP2 ADC) for 2L+ EGFRmt mNSCLC (after EGFR TKI) with a PDUFA date set to July 12, 2025.
- The application was based on data from the P2 TROPION-Lung05 trial of Dato with supporting data from P3 TROPION-Lung-01 (EGFRm subset) as well as P1 TROPION-PanTumor01
- AZ/Daiichi shared a pooled analysis of previously treated EGFRmt NSCLC patients from the P2 TL-05 and P3 TL-01 studies at ESMO Asia 2024, showing ORR of 43% and mDOR of 7.0 mo
- The PDUFA date is set for Jul 2025, in line with CI expectations of approval in ~Q3’25, but approval could be granted earlier given that Dato-DXd has breakthrough therapy designation and priority review
- Timing of this update was also as expected, given announcement of the BLA submission in Nov 2024
- AZ has previously stated that the ongoing P3 TROPION-Lung15 trial of Dato-DXd +/- osimertinib vs platinum-based doublet chemo in 2-3L EGFRm la/mNSCLC who have progressed on osi will serve as the confirmatory study
- Dato-DXd's 2L+ EGFRmt mNSCLC program does not directly compete with Gilead programs. However, Dato-DXd is a high threat competitor in 1L mNSCLC, and an accelerated approval would confirm its position as the first-to-market TROP2 ADC in mNSCLC in the US though initially in a narrowed addressable population (EGFRmt est. ~16%)
- Approval could help AZ build momentum for Dato-DXd ahead of upcoming high priority datasets in 1L NSCLC including P3 AVANZAR (Dato-DXd + durva + chemo vs pembro + chemo in 1L Nsq mNSCLC) in H2 2025
- With an approval, Dato-DXd will also beat Merck's sacituzumab tirumotecan (sac-TMT; TROP2 ADC) to market including in the EGFRmt space where Merck currently has two ongoing P3 trials for sac-TMT in the 2L+ and 3L+ setting (TroFuse-004 and TroFuse-009; also recently granted BTD for 2L+ EGFRmt mNSCLC after TKI and chemo)